We propose to study cellular alterations in the lung which might occur and accompany the well-known pulmonary congestion and edema with endotoxemia. Endotoxin has been shown to affect cell membranes and to interfere with oxidative cell metabolism in organs other than the lung. We would study membrane functions such as permeability to Na ion, K ion and Cl minus, active Na minus K ions transport and membrane-linked enzymes, Na ion, K ion-ATPase, adenylate cyclase. Cellular energy yielding processes will be assessed by measuring contents of energy-related adenine nucleotides, studying mitochondrial respiratory functions, and by assaying enzymes related to aerobic lactate production. We have previously studied these cellular functions in liver and in lung by control animals and/or animals subjected to hemorrhagic shock. We therefore have, in most instances methodologies worked out for a detailed study of lung cells with endotoxemia. In order to distinguish effects of endotoxemia on the endothelial cells from those on other cells of the lung, we propose to isolate and culture the pulmonary endothelial cells prior to cellular measurements. We would also study endotoxin-related changes in the type II alveolar epithelial cellls isolated from lungs. We plan further to study possible effects of endotoxemia on the cellular ion and water transport capability of the tracheobronchaial epithelial cells. This would be studied by measuring the short-circulating current and ion fluxes across the tracheal wall. Such measurements would allow us to evaluate changes in the ability of the tracheobronchial epithelial membranes to actively secrete water into the tracheobronchial lumen, a function which could determine the fluidity of the mucosal secretions in the airways. Cellular studies of effects of endotoxing would be carried out in intact animals as well as in isolated perfused lungs to possibly separate the direct effects of endotoxin from those that are mediated via the formed elements of the blood. The studies will contribute to our understanding of cellular problems that might be occurring in the lung with sepsis.